ACDC: Analysis of Congruent Diversification Classes

Diversification rates inferred from phylogenies are not identifiable. There are infinitely many combinations of speciation and extinction rate functions that have the exact same likelihood score for a given phylogeny, building a congruence class. The specific shape and characteristics of such congruence classes have not yet been studied. Whether speciation and extinction rate functions within a congruence class share common features is also not known. Instead of striving to make the diversification rates identifiable, we can embrace their inherent non-identifiable nature. We use two different approaches to explore a congruence class: (i) testing of specific alternative hypotheses, and (ii) randomly sampling alternative rate function within the congruence class. Our methods are implemented in the open-source R package ACDC (https://github.com/afmagee/ACDC). ACDC provides a flexible approach to explore the congruence class and provides summaries of rate functions within a congruence class. The summaries can highlight common trends, i.e. increasing, flat or decreasing rates. Although there are infinitely many equally likely diversification rate functions, these can share common features. ACDC can be used to assess if diversification rate patterns are robust despite non-identifiability. In our example, we clearly identify three phases of diversification rate changes that are common among all models in the congruence class. Thus, congruence classes are not necessarily a problem for studying historical patterns of biodiversity from phylogenies.

EXPRESS: The psychological role of music and attentional control for religious experiences in worship

This study investigated the psychological dynamics during worship experiences under the influence of different music conditions. 60 believers were recruited to participate in experiments where they were asked to engage in worship and to connect with God while continuously ranking how strongly they sensed the presence of the divine. After each condition, they were asked to rate how well they were able to focus on God during the worship procedure. Based on a previously published feedback loop model that portrays global psychological mechanisms in worship, we deduced two hypotheses: (i) the ability to focus on God is positively associated with how strong the subjective religious experience becomes; (ii) and the different musical conditions yield varying degrees in the intensity of the felt presence of God. Our statistical analyses on the current sample demonstrate that both alternative hypotheses can be accepted. For the latter thesis, two further assumptions were at play: (a) we speculated that religious worship songs were associated with stronger divine experiences than with secular ones; and (b) it was assumed that if they could worship to their own selection of songs, the experience would be more powerful than with the ones that were provided by the research team. Whereas upon our investigation the former assumption can be deemed correct, the latter shows a positive but insignificant association.

Preparing to move: Setting initial conditions to simplify interactions with complex objects

Humans dexterously interact with a variety of objects, including those with complex internal dynamics. Even in the simple action of carrying a cup of coffee, the hand not only applies a force to the cup, but also indirectly to the liquid, which elicits complex reaction forces back on the hand. Due to underactuation and nonlinearity, the object’s dynamic response to an action sensitively depends on its initial state and can display unpredictable, even chaotic behavior. With the overarching hypothesis that subjects strive for predictable object-hand interactions, this study examined how subjects explored and prepared the dynamics of an object for subsequent execution of the target task. We specifically hypothesized that subjects find initial conditions that shorten the transients prior to reaching a stable and predictable steady state. Reaching a predictable steady state is desirable as it may reduce the need for online error corrections and facilitate feed forward control. Alternative hypotheses were that subjects seek to reduce effort, increase smoothness, and reduce risk of failure. Motivated by the task of ‘carrying a cup of coffee’, a simplified cup-and-ball model was implemented in a virtual environment. Human subjects interacted with this virtual object via a robotic manipulandum that provided force feedback. Subjects were encouraged to first explore and prepare the cup-and-ball before initiating a rhythmic movement at a specified frequency between two targets without losing the ball. Consistent with the hypotheses, subjects increased the predictability of interaction forces between hand and object and converged to a set of initial conditions followed by significantly decreased transients. The three alternative hypotheses were not supported. Surprisingly, the subjects’ strategy was more effortful and less smooth, unlike the observed behavior in simple reaching movements. Inverse dynamics of the cup-and-ball system and forward simulations with an impedance controller successfully described subjects’ behavior. The initial conditions chosen by the subjects in the experiment matched those that produced the most predictable interactions in simulation. These results present first support for the hypothesis that humans prepare the object to minimize transients and increase stability and, overall, the predictability of hand-object interactions.

Early knapping techniques do not necessitate cultural transmission

Early stone tools are claimed to be the earliest evidence for the cultural transmission of toolmaking techniques, and with it, cumulative culture. This claim has ostensibly been supported by experimental studies wherein modern humans learned stone tool production (knapping) in conditions that provided opportunities for cultural transmission. However, alternative hypotheses propose that individual learning was sufficient for the expression of early knapping techniques. In order to evaluate this possibility, the capacities of individuals to independently re-innovate early knapping techniques need to be determined. For this, individuals must be tested in cultural isolation, i.e., in a test condition in which knapping techniques cannot be culturally transmitted via demonstrations or reverse engineering. Here, we report on the results of this test condition with human participants (N = 28). Naïve individuals spontaneously re-innovated various early knapping techniques, resulting in products resembling the earliest core and flake technologies. These results contradict previous hypotheses and conclusions of earlier experiments that explicitly implicated cultural transmission in Oldowan stone tool production. They suggest instead that knapping techniques among pre-modern hominins could have been individually derived rather than necessitating cultural transmission.

Allosteric regulation of the proteasomes catalytic sites by the proteasome activator PA28gamma/REGgamma

Proteasome Activator 28γ (PA28γ) is a member of the 11S family of proteasomal regulators that is constitutively expressed in the nucleus and is implicated in certain cancers, lupus, rheumatoid arthritis, and Poly-glutamine neurodegenerative diseases. However, how PA28γ functions in protein degradation remains unclear. Though PA28γs mechanism has been investigated for some time, many alternative hypotheses have not been tested: e.g. 1) substrate selection, 2) allosteric upregulation of the Trypsin-like catalytic site, 3) allosteric inhibition of the Chymotrypsin- and Caspase-like catalytic sites, 4) conversion of the Chymotrypsin- or Caspase-like sites to new Trypsin-like catalytic sites, and 5) gate-opening in combination with these. The purpose of this study was to conclusively determine how PA28γ regulates proteasome function. Here, we rigorously and definitively show that PA28γ uses an allosteric mechanism to upregulate the proteolytic activity of the 20S proteasomes Trypsin-like catalytic site. Using a constitutively open channel proteasome, we were able to dissociate gating affects from catalytic affects demonstrating that the PA28γ-increases the affinity (Km) and Vmax for Trypsin-like peptide substrates. Mutagenesis of PA28γ also reveals that it does not select for (i.e. filter) peptide substrates, and does not change the specificity of the other active sites to trypsin-like. Further, using Cryo-EM we were able to visualize the C7 symmetric PA28γ-20S proteasome complex at 4.4A validating it's expected 11S-like quaternary structure and proteasome binding mode. The results of this study provide unambiguous evidence that PA28γ functions by allosterically upregulating the T-L like site in the 20S proteasome.

Statistical reproducibility for pairwise t-tests in pharmaceutical research

This paper investigates statistical reproducibility of the [Formula: see text]-test. We formulate reproducibility as a predictive inference problem and apply the nonparametric predictive inference method. Within our research framework, statistical reproducibility provides inference on the probability that the same test outcome would be reached, if the test were repeated under identical conditions. We present an nonparametric predictive inference algorithm to calculate the reproducibility of the [Formula: see text]-test and then use simulations to explore the reproducibility both under the null and alternative hypotheses. We then apply nonparametric predictive inference reproducibility to a real-life scenario of a preclinical experiment, which involves multiple pairwise comparisons of test groups, where different groups are given a different concentration of a drug. The aim of the experiment is to decide the concentration of the drug which is most effective. In both simulations and the application scenario, we study the relationship between reproducibility and two test statistics, the Cohen’s [Formula: see text] and the [Formula: see text]-value. We also compare the reproducibility of the [Formula: see text]-test with the reproducibility of the Wilcoxon Mann–Whitney test. Finally, we examine reproducibility for the final decision of choosing a particular dose in the multiple pairwise comparisons scenario. This paper presents advances on the topic of test reproducibility with relevance for tests used in pharmaceutical research.

Why Does Cognitive Reserve Align With Modern Western Ideals of Success? Theoretical & Methodological Proposals

Cognitive reserve (CR) is a framework that investigates discrepancies between brain pathology and cognitive decline. In explaining why individuals with similar levels of brain pathology display different levels of functional impairment, CR research focuses on factors that resemble modern, Western ideals of success: greater education, professional achievement, a self-directed life, and physically and intellectually stimulating leisure time. This theoretical paper documents this alignment between CR and modern, Western ideals of success to hypothesize different mechanisms by which CR may operate. The focus in the CR literature has been on investigating and operationalizing the direct cognitive changes that come from intellectual cultivation, and the native abilities that are hypothesized to produce differences in both education and cognitive outcomes. This paper argues that an attention to CR’s relationship to current definitions of success presents alternative hypotheses about the mechanisms by which CR operates. Specifically, the paper outlines two potential mechanisms and frames alternative means of studying them: First, does the accrual of CR simply follow from being successful in conventional ways because of the material benefits of wealth and stability that success brings? Second, does a lack of success carry cognitive risks solely because of material deprivation, or are there additional psychosocial penalties that come from living a non-normative life—especially when that is not of one’s choosing? This paper proposes both cross-cultural and intersectional methods to begin to better understand the relationship between normative success and cognitive health.

Subjective Age Changes During the COVID-19 Pandemic

Aging is associated with an increased risk of COVID-19 morbidity and mortality. In this study, we tested whether the pandemic influenced how old individuals felt by examining longitudinal within-person changes in subjective age. We tested two alternative hypotheses: (a) people felt increasingly older in response to the stress generated by COVID-19; (b) people felt increasingly younger due to psychological distancing from older age. We tested these hypotheses in a large US sample of adults assessed once before and twice during the COVID-19 pandemic. Multilevel analyses indicated that people reported feeling younger with the emergence of COVID-19. We further tested demographic, health, and psychosocial predictors of changes in subjective age. Overall, the findings supported the hypothesis that subjective age partly reflects a coping process of psychological distancing from older age, a process that parallels physical and social distancing.

Explaining Membership Eligibility

This chapter elaborates the book’s argument on the nature of regional communities, the contestation and evolution of membership norms, how these norms shape a regional community’s decision-making on which non-member states are eligible to join, and what happens when membership norms break down. It compares this argument to alternative hypotheses with observable implications derived from existing theories of regional integration.